Single-Cell Immune Mapping of Melanoma Sentinel Lymph Nodes Reveals an Actionable Immunotolerant Microenvironment.

Autor:	Yaddanapudi K; Immuno-Oncology Group, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.; Department of Surgery, Division of Immunotherapy, University of Louisville, Louisville, Kentucky.; Department of Microbiology/Immunology, University of Louisville, Louisville, Kentucky., Stamp BF; Immuno-Oncology Group, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.; Department of Surgery, Division of Immunotherapy, University of Louisville, Louisville, Kentucky., Subrahmanyam PB; Institute for Immunity, Transplantation and Infection, Stanford School of Medicine, Stanford, California., Smolenkov A; James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky., Waigel SJ; Department of Medicine, University of Louisville, Louisville, Kentucky., Gosain R; James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky., Egger ME; James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.; Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky., Martin RCG; Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky., Buscaglia R; Department of Mathematics and Statistics, Northern Arizona University, Flagstaff, Arizona., Maecker HT; Institute for Immunity, Transplantation and Infection, Stanford School of Medicine, Stanford, California., McMasters KM; Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky., Chesney JA; Immuno-Oncology Group, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.; Department of Surgery, Division of Immunotherapy, University of Louisville, Louisville, Kentucky.; Department of Medicine, University of Louisville, Louisville, Kentucky.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 May 13; Vol. 28 (10), pp. 2069-2081.
DOI:	10.1158/1078-0432.CCR-21-0664
Abstrakt:	Purpose: Improving our understanding of the immunologic response to cancer cells within the sentinel lymph nodes (SLN) of primary tumors is expected to identify new approaches to stimulate clinically meaningful cancer immunity. Experimental Design: We used mass cytometry by time-of-flight (CyTOF), flow cytometry, and T-cell receptor immunosequencing to conduct simultaneous single-cell analyses of immune cells in the SLNs of patients with melanoma. Results: We found increased effector-memory αβ T cells, TCR clonality, and γδ T cells selectively in the melanoma-bearing SLNs relative to non-melanoma-bearing SLNs, consistent with possible activation of an antitumor immune response. However, we also observed a markedly immunotolerant environment in the melanoma-bearing SLNs indicated by reduced and impaired NK cells and increased levels of CD8+CD57+PD-1+ cells, which are known to display low melanoma killing capabilities. Other changes observed in melanoma-bearing SLNs when compared with non-melanoma-bearing SLNs include (i) reduced CD8+CD69+ T cell/T regulatory cell ratio, (ii) high PD-1 expression on CD4+ and CD8+ T cells, and (iii) high CTLA-4 expression on γδ T cells. Conclusions: Our data suggest that these immunologic changes compromise antimelanoma immunity and contribute to a high relapse rate. We propose the development of clinical trials to test the neo-adjuvant administration of anti-PD-1 antibodies prior to SLN resection in patients with stage III melanoma. See related commentary by Lund, p. 1996. (©2022 American Association for Cancer Research.)
Databáze:	MEDLINE
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